scholarly journals Clinical Utility of Noninvasive Prenatal Screening for Rare Chromosome Abnormalities in Singleton Pregnancies

2021 ◽  
Author(s):  
Ting Hu ◽  
Jiamin Wang ◽  
Qian Zhu ◽  
zhu zhang ◽  
Rui Hu ◽  
...  
Keyword(s):  
Incidental Findings ◽  
Clinical Utility ◽  
Prenatal Screening ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome Abnormalities ◽  
Predictive Values ◽  
Noninvasive Prenatal Screening ◽  
The Common ◽  
Fetal Aneuploidies

Objective: To systematically investigate the clinical utility of noninvasive prenatal screening (NIPS) commercially used for the common fetal aneuploidies as a prenatal screening tool for rare chromosome abnormalities (RCAs). Design: Prospective study. Setting: Hospital-based. Population or Sample: 528 gravidas with positive NIPS results for RCAs. Methods: Gravidas with positive NIPS results for RCAs subsequently underwent amniocentesis for single nucleotide polymorphism array (SNP-array) were recruit. The degrees of concordance between NIPS and SNP-array were classified into full concordance, partial concordance, discordance related and discordance. Main Outcome Measures: The positive predictive values (PPVs) for rare aneuploidies and segmental imbalances, while incidental findings for regions of homozygosity/uniparental disomy (ROH/UPD), were used to evaluate the performance of NIPS. Results: Of the 528 gravidas with positive NIPS results, 29.2% were confirmed with positive prenatal SNP-array results (154/528). The PPVs for rare aneuploidies and segmental imbalances were 6.1% (7/115) and 21.1% (87/413), respectively. ROH/UPDs, as incidental findings, have been identified in 9.5% (50/528) of gravidas with positive NIPS results. The PPV for clinical significant findings was 8.9% (47/528), including 7 cases with mosaic rare aneuploidies, 35 with pathogenic/likely pathogenic copy number variants, and 5 with imprinting disorders. Conclusions: NIPS commercially used for the common fetal aneuploidies yielded low PPV for rare aneuploidies, moderate PPV for segmental imbalances, and incidental findings for ROH/UPD. For the low PPV for clinical significant findings, NIPS has limited clinical utility for RCAs. Prenatal SNP-array should be regarded as the first-tier test for positive NIPS, particularly for those involved imprinted chromosomes.

scholarly journals Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunyun Liu ◽  
Xiaosha Jing ◽  
Lingling Xing ◽  
Sha Liu ◽  
Jianlong Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Prenatal Screening ◽  
Sex Chromosome ◽  
Nasal Bone ◽  
Low Risk ◽  
Trisomy 13 ◽  
Second Trimester ◽  
Predictive Values ◽  
Noninvasive Prenatal Screening ◽  
Hypoplastic Nasal Bone

Background: We aimed to assess the clinical application of noninvasive prenatal screening (NIPS) based on second-trimester ultrasonographic soft markers (USMs) in low-risk pregnant women.Methods: Data of pregnant women between April 2015 and December 2019 were retrospectively analyzed. Pregnant women [age at expected date of confinement (EDC) of <35 years; low risks for trisomy 21 (T21) and trisomy 18 (T18) based on maternal serum screening; presenting second-trimester USMs (7 types)] who successfully underwent NIPS and had available follow-up information were included in our study. Cases with positive NIPS results were prenatally diagnosed. All patients were followed up for 6 months to 2 years after NIPS, and their clinical outcomes were obtained. Subgroup analyses were performed according to the different USMs.Results: NIPS suggested that among a total of 10,023 cases, 37 (0.37%) were at high risk of aneuploidy, including 4 T21, 6 trisomy 13 (T13), and 27 sex chromosome abnormalities (SCA). Ten cases with aneuploidy (0.10%) were confirmed by prenatal diagnosis, consisting of two T21 and eight SCA. The eight fetuses with SCA consisted of one monosomy X, two XXY, one XXXY, one XXX, one XYY, and two mosaicisms. T21 was detected in one fetus with absent or hypoplastic nasal bone and one fetus with echogenic intracardiac focus (EICF). SCA was detected in five fetuses with EICF, two fetuses with multiple soft markers, and one fetus with echogenic bowel. The positive rate of chromosomal aneuploidy was significantly higher in fetuses with absent or hypoplastic nasal bone (6.25 vs. 0.10%, p = 0.017), echogenic bowel (3.7 vs. 0.10%, p = 0.029), and multiple soft markers (0.678 vs. 0.10%, p = 0.045) than in the total fetuses. The positive predictive values (PPVs) of NIPS in these three groups were 100%, 50%, and 100%, respectively. EICF accounted for 93.25% (9,346/10,023) of the study population, whereas the PPV of NIPS was only 20%.Conclusion: NIPS is an advanced screening test for low-risk pregnant women. In the 10,023 pregnant women sampled, SCA were more common than autosomal trisomy, and EICF was the most frequent USM but the least predictive aneuploidy. Further aneuploidy evaluation is suggested for low-risk pregnant women whose ultrasound indicates absent or hypoplastic nasal bone, echogenic bowel, or multiple soft markers. NIPS can serve as a second-line complementary screening for these women.

Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes

2019 ◽  
Vol 21 (9) ◽  
pp. 1998-2006 ◽  
Author(s):  
Desheng Liang ◽  
David S. Cram ◽  
Hu Tan ◽  
Siyuan Linpeng ◽  
Yingdi Liu ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Prenatal Screening ◽  
Noninvasive Prenatal Screening

Noninvasive prenatal screening for aneuploidy: positive predictive values based on cytogenetic findings

2015 ◽  
Vol 213 (2) ◽  
pp. 214.e1-214.e5 ◽  
Author(s):  
Jeanne M. Meck ◽  
Elizabeth Kramer Dugan ◽  
Ludmila Matyakhina ◽  
Ayala Aviram ◽  
Carolyn Trunca ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Predictive Values ◽  
Noninvasive Prenatal Screening

scholarly journals Efficiency of Non-invasive Prenatal Screening in Pregnant Women at Advanced Maternal Age

2020 ◽  
Author(s):  
Hui Zhu ◽  
Xiaoxiao Jin ◽  
Yuqing Xu ◽  
Weihua Zhang ◽  
Xiaodan Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Predictive Value ◽  
Trisomy 21 ◽  
Maternal Age ◽  
Prenatal Screening ◽  
Screening Method ◽  
Advanced Maternal Age ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Screening ◽  
Fetal Aneuploidies

Abstract Background: To evaluate the efficiency of noninvasive prenatal screening (NIPS) in the prenatal screening for fetal aneuploidies in pregnant women at advanced maternal age (AMA). Results: From February 1, 2015, to December 31, 2018, 29,443 pregnant women at AMA underwent NIPS and followed-up were recruited. Their detailed clinical data and follow-up outcomes were collected and analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of NIPS for detecting fetal trisomy 21 were 99.11%, 99.96%, 90.98%, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100%, 99.94%, 67.92%, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100%, 99.96%, 27.78%, and 100%, respectively. The prevalence of fetal trisomy 21 increased with maternal age. There were significant differences in the prevalence of fetal trisomy 21 among the groups I (35-37-year-old), II (38-40-year-old) and III (41-year-old and older) ( P <0.05). Conclusion: It is indicated that NIPS is an effective prenatal screening method in pregnant women at AMA. Keywords: Advanced maternal age, Trisomy, Noninvasive prenatal screening, Fetal aneuploidies , Prenatal screening method

Whole Genome 250K SNP Array Allows for Detection of Previously Unidentified Lesions in Chromosome 5 in Patients with MDS.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2350-2350
Author(s):  
Lukasz P. Gondek ◽  
Abdo Haddad ◽  
Mikkael A. Sekeres ◽  
Yasuhito Nannya ◽  
Seishi Ogawa ◽  
...  
Keyword(s):  
Snp Array ◽  
Uniparental Disomy ◽  
Genome Scan ◽  
Chromosome Abnormalities ◽  
Gene Copy ◽  
Whole Genome ◽  
Chromosome 5 ◽  
Therapeutic Success ◽  
Molecular Therapeutics ◽  
Whole Genome Scan

Abstract Chromosome abnormalities in myelodysplastic syndromes (MDS) have important prognostic implications. The frequent occurrence of certain invariant aberrations implies a role of involved genes in the malignant phenotype of the affected clone. The recent therapeutic success of lenalidomide (CC-5013, Revlimid® ) in achieving cytogenetic remissions in a high proportion of patients with the 5q deletion suggests that certain chromosomal lesions may be used to guide targeted molecular therapeutics. Nevertheless, traditional metaphase cytogenetics (MC) has limited resolution and is hampered by frequent lack of growth in vitro. Due to the inherent insensitivity of banding techniques ( > 20% of abnormal metaphases), only large clones can be detected. Significance of FISH-based detection of a few karyotypically abnormal cells remains unclear as smaller clones may be transient and therefore not pathogenic. Whole genome scan using SNP arrays (SNP-A) allows for precise detection of cryptic (due to limited size) defects by simultaneous analysis of LOH and gene copy number. Unlike MC, uniparental disomy (UPD) can be easily detected by SNP-A. The resolution level of this technology is limited only by the density of the arrays; currently 500K SNP-A are readily available. We hypothesized that the application of SNP-A in MDS will allow for the detection of "marker" lesions located within chromosomal regions frequently affected in MDS. In patients with deletion 5q, standard MC analyses have shown that additional chromosome abnormalities impart an incremental adverse prognosis in the absence of marrow blast elevation, suggesting that detection of occult lesions may have immediate prognostic relevance. Here, we applied 250K Affymetrix SNP-A for bone marrow karyotyping. Results were confirmed using microsatellite analysis. Initially, we have analyzed a cohort of 356 MDS patients, 43 patients had losses of genomic material in chromosome 5. While studying a subset of patients (N=112) from this cohort by SNP-A, we confirmed 13/15 previously known 5q31 deletions. In addition, we identified 2 patients with aberrations involving this region that were not detected by MC. One patient had a segmental UPD5q23.3-q31.1, likely due to mitotic recombination, while the second patient with uninformative cytogenetics had a new deletion within 5q. The affected regions involved the cytokine gene cluster at 5q31. The SNP-A-based whole genome scan of patients with previously known 5q aberrations as the sole MC-defined abnormality detected additional deletions present in other chromosomes in 3/7 patients. These lesions were located at 1p21.1, 2q21.2, 4q23, 6p21.33, 7q34, 8q24.23 and 11p15.1. Our findings may point towards rational application of lenalidomide in patients who would otherwise not be primary targets of such therapy. Moreover, as the response rate to lenalidomide is not complete and some patients may relapse, it is possible that detection of certain occult defects using SNP-A may point towards lenalidomide resistance or modify clinical features in individual patients.

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